CLS 442 RBC Lecture 3 Part 2 (Partial)

Acute hemolytic anemia is sudden, episodic, or paroxysmal. What are 3 examples?

• Paroxysmal Nocturnal Hemoglobinuria(PNH)

• Paroxysmal Cold Hemoglobinuria(PCH)

• Acute Hemolytic Transfusion Reaction(AHTR)

Chronic hemolytic anemia has no anemia as long as BM can compensate. What are 2 examples?

• G6PD deficiency

• thalassemia. major

thalassemia major is chronic but so severe that the _____ can’t compensate

bone marrow

acquired (HA) definition

exposed to an agent that induces hemolysis, such as malaria

inherited (HA) definition

a mutant gene which causes hemolysis is passed on to offspring, such as thalassemia

Intrinsic RBC defects are mostly ________

inherited

Intrinsic RBC defects are common in _____,_____, and ______

• RBC membrane

• metabolism

• Hb content (hemoglobinopathies)

Extrinsic RBC defects are mostly _________

acquired

Extrinsic RBC defects can be due to what? (5)

• malaria

• drugs

• immune hemolysis

• trauma

• microangiopathic(MAHA: TTP, HUS, DIC)

what RBC defect is intrinsic but acquired

PNH

What can be seen in intravascular hemolysis? (3)

• RBC fragmentation (DIC, heart prosthetic valves)

extravascular hemolysis is ______-mediated

macrophage

Extravascular hemolysis is in the _____, _______ or ________

macrophage, BM, and Liver

what site of hemolysis is the following results:

• total bilirubin-

• indirect bilirubin-

• direct conjugated bilirubin-WRI

• LDH-

• Haptoglobin-

• Free hgb-

• hemopesin-

• Urobiliongen-

• Free hgb -

• methemoglobin-

• Prussian blue staining or urine sediment-

• hgb, hct, rbc count-

• schistocytes-

• spherocytes-

• total bilirubin- ↑

• indirect bilirubin- ↑

• direct conjugated bilirubin-WRI

• LDH-↑

• Haptoglobin-↓

• Free hgb-↑

• hemopesin-↑

• Urobiliongen-↑

• Free hgb - +

• methemoglobin- +

• Prussian blue staining or urine sediment- +

• hgb, hct, rbc count- ↓

• schistocytes-present

• spherocytes- absent

what site of hemolysis is the following results:

• total bilirubin-

• indirect bilirubin-

• direct conjugated bilirubin-WRI

• LDH-

• Haptoglobin-

• Free hgb-

• hemopesin-

• Urobiliongen-

• Free hgb -

• methemoglobin-

• Prussian blue staining or urine sediment-

• hgb, hct, rbc count-

• schistocytes-

• spherocytes-

• total bilirubin- ↑

• indirect bilirubin- ↑

• direct conjugated bilirubin-WRI

• LDH-sl↑

• Haptoglobin-sl↓

• Free hgb-sl↑

• hemopesin-↑

• Urobiliongen-↑

• Free hgb - +

• methemoglobin- +

• Prussian blue staining or urine sediment- +

• hgb, hct, rbc count- ↓

• schistocytes-absent

• spherocytes- present

what is hereditary spherocytosis?

mutations in proteins which maintain vertical attachments

in hereditary spherocytosis, RBCs lose _______, destroyed by the spleen leading to _______, or some RBCs may endure further membrane modifications forming ________

• Surface area,

• EV hemoylsis

• microscherocytes

what is the triad of hereditary spherocytosis

• anemia, splenomegaly, and jaudnice

on a PBS for hereditary spherocytosis, what are the hallmarks (2)

• spherocytosis

• increased reticulocytosis= polychromasia

what do the RBC indices read in hereditary spherocytosis?

• high MCHC

• high CHCM

reticulocytosis is indicative of ______

polychromasia

high CHCM indcates _______ RBCS

hyperdense

what is highly suggestive of HS?(3)

childhood hemolytic anemia, family history of similar abnormalities, uniform spherocytes

what is the definitive diagnosis of hereditary spherocytosis?(5)

• family history of HS

• splenemegaly

• high MCHC

• reticulocytosis

• spherocytes

if required, what tests can be done for hereditary spherocytosis and their expected results

• osmotic fragility test (↑)

• eosin-5’-maleimide binding test(↓)

what is the DAT result for hereditary spherocytosis?

negative

what is the severe form of hereditary elliptocytosis?

hereditary pyropoiklocytosis(HPP)

what is the expected findings for hereditary pyropoikilocytosis?(5)

• extreme poikilocytosis

• very low MCV

• fragmentation

• microspherocytosis

• elliptocytosis (similar to burns)

what is overhydrated hereditary stomatocytosis?

• def. in stomatin protein or mutation in RhAG protein

what is dehydrated hereditary stomatocytosis or hereditary xerocytosis

defect in membrane cation permeability= dehydrated RBCs

is this test result extravascular or intravascular?

serum haptoglobin- decreased

urine hemoglobin- negative

urine sediment prussian blue stain- negative

extravascular

is this test result extravascular or intravascular?

serum haptoglobin- decreased

urine hemoglobin- postive

urine sediment prussian blue stain- positive

intravascular

what is paroxysmal nocturnal hemoglobinuria?

acquired; RBCs lack CD55 and CD59= RBCS susceptible to spontaneous lysis by complement

what is PNH type 1

normal level of CD55 and CD59, little to no lysis

what is PNH type 2

partial CD55 and CD59 def; relatively resistant to lysis

what is PNH type 3

complete deficiency of CD55 and CD59, highly sensitive to lysis

what is the most common RBC types in PNH

combination of 1 and 3

what is the confirmatory test of PNH

detection of CD55 and CD59 by flowcytometry

what is G6PD deficiency

G6PD enzyme missing = no protection for RBC from oxidase

what is the most common RBC enzyme defect?

G6PD deficiency

African males with G6PD (A- variant) are protected against what?

plasmodium falciparum malaria

what class of G6PD deficiency is this?

• <1% activity

• chronic hereditary nonspherocytic hemolytic anemia, serverity is variable, rare

class I

what are examples of class I gp6d def.

• G6PD-serres

• G6PD-Madrid

what class of G6PD deficiency is this?

• <10% activity

• severe episodic acute hemolytic anemia associated with infections, certain drug, and fava beans

• not self limited and may require transfusions during hemoyltic episodes

class II

what are examples of class 2 g6pd def.

• G6PD-Mediterrenean

• G6PD-Chatham

what class of G6PD deficiency is this?

• % activity

• episodic acute hemoyltic anemia, associated with infections and certain drugs

class III

what are examples of class III g6pd def.

• G6PD A-

• G6PD-Canto

what class of G6PD deficiency is this?

• 60-150%

class IV

What are examples of class IV g6pd def.

• G6PD-B

• G6PD-A+

what are triggers of acute hemolytic anemia in G6PD def?(3)

• oxidising drugs

• infections

• fava beans

what will the CBC show for severe G6PD def? (6)

• anemia (moderate to severe

• normochromic/normocytic

• marked anisocytosis

• poikilocytosis

• spherocytosis

• schistocytosis

what will the PBS show for G6PD def

• bite cells

• heinze bodies(supravital staining)

in common G6PD def, what can be seen in the CBC(5)

• profound reticulocytosis

• low serum haptoglobin

• high indirect bili

• high LDF

• increased plasma Hb

what is PK deficiency

causes premature destruction of RBCS and depletion of ATP results in lack of membrane integrity

what is the clinical presentation of PK def. (4)

• anemia

• jaundice

• splenomegaly

• gallstones(chronic hemolysis)

what is will be seen on PBS for PK def?

burr cells

IgM mediated hemolysis can result in extravascular hemo., intravascular hemo., or both?

both

IgG mediated hemolysis can result in extravascular hemo., intravascular hemo., or both?

extravascular(RBCS removed by macrophages in spleen/liver

what is the confirmatory test for immune hemoyltic anemia?

DAT postive

what is the most common type of autoimmune hemolytic anemia?

warm autoimmune hemolytic anemia

what is this autoimmune hemolytic anemia?

Immunoglobulin- IgG

Optimum reactivity temperature of autoantibody- 37 C

Sensitization detected by DAT-IgG or IgG + complement

Complement activation- variable

Hemolysis- Extravascular

Autoantibody specificity- Panreactive

Other lab findings- polychromasia, spherocytes

WAIHA

what is this autoimmune hemolytic anemia?

Immunoglobulin-IgM

Optimum reactivity temperature of autoantibody-4 C

Sensitization detected by DAT-Complement

Complement activation- Yes

Hemolysis- EV, sometimes IV

Autoantibody specificity-I(most), i(some), Pr(rare)

Other lab findings- can see RBC agglutination, hemoglobunira

Cold agglutinin disease (CAD)

In CAIHA, IgM autoantiboies bind RBCs when patient exposed to ___________

cold temps

what is this autoimmune hemolytic anemia?

Immunoglobulin- IgG

Optimum reactivity temperature of autoantibody-4 C

Sensitization detected by DAT- Complement

Complement activation- Yes

Hemolysis- IV

Autoantibody specificity- P

Other lab findings- polychromasia, spherocytes, schistocytes, NRBCS, ansiocytes, poikilocytosis, hemoglobinuria, Anti-P positive

Paroxysmal Cold Hemoglobunira(PCH)

Paroxysmal Cold Hemoglobinuria is usually caused by ______. Autoantibody binds the P antigen on RBCs in cold temps and partially activates complement BUT fully activates complement at warm temps thus exhibiting _________

• Anti-P

• intravascular hemolysis

Paroxsymal Cold Hemoglobinuria is most commonly seen in young children after ____________

viral respiratory infection